McKenna's Pharmacology for Nursing, 2e

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P A R T 6  Drugs acting on the endocrine system

insulin binding to insulin receptors and may actually increase the number of insulin receptors. They are indic­ ated as an adjunct to diet and exercise to lower blood glucose levels in type 2 diabetes mellitus. They have the off-label use of being an adjunct to insulin to improve glucose control in type 2 diabetics. Pharmacokinetics These drugs are rapidly absorbed from the GI tract and undergo hepatic metabolism. They are excreted in the urine. The peak effects and duration of effects differ because of the activity of various metabolites of the dif- ferent drugs. Contraindications and cautions Sulfonylureas are contraindicated in the presence of known allergy to any sulfonylureas to avoid hypersensitiv- ity reactions and in diabetes complicated by fever, severe infection, severe trauma, major surgery, ketoacidosis, severe renal or hepatic disease, pregnancy or breastfeed- ing, which require tighter control of glucose levels using insulin. These drugs are also contraindicated for use in type 1 diabetes mellitus, who do not have functioning beta cells and would have no benefit from the drug . These drugs are not for use during pregnancy. Insulin should be used if a hypoglycaemic agent is needed during pregnancy. Some of these drugs cross into breast milk, and adequate studies are not available on others. Because of the risk of hypoglycaemic effects in the baby , these drugs should not be used during breast- feeding. Another method of feeding the baby should be used. The safety and efficacy of these drugs for use in children have not been established. Adverse effects The most common adverse effects related to the sulfo- nylureas are hypoglycaemia (caused by an imbalance in levels of glucose and insulin) and GI distress, includ- ing nausea, vomiting, epigastric discomfort, heartburn and anorexia. (Anorexia should be monitored because affected individuals may not eat after taking the sulfony- lurea, which could lead to hypoglycaemia.) Allergic skin reactions have been reported with some of these drugs and, as mentioned earlier, there may be an increased risk of cardiovascular mortality, particularly with the first-generation agents. Clinically important drug–drug interactions Care should be taken with any drug that acidifies the urine because excretion of the sulfonylurea may be decreased. Caution should also be used with beta- blockers, which may mask the signs of hypoglycaemia, and with alcohol, which can lead to altered glucose levels when combined with sulfonylureas. Caution must

also be used with many herbal therapies that could alter blood glucose levels.

Prototype summary: Glibenclamide Indications: Adjunct to diet and exercise in the management of type 2 diabetes; with metformin or insulin for stabilisation of diabetic people. Actions: Stimulates insulin release from functioning beta cells in the pancreas; may improve insulin binding to insulin receptor sites or increase the number of insulin receptor sites. Pharmacokinetics: Route Onset Duration Oral 1 hour 24 hours T 1/2 : 4 hours; metabolised in the liver and excreted in bile and urine. Adverse effects: GI discomfort, anorexia, nausea, vomiting, heartburn, diarrhoea, allergic skin reactions, hypoglycaemia. O ther oral hypoglycaemic agents Several other oral hypoglycaemic agents are available. Although these drugs are structurally unrelated to the sulfonylureas, they are frequently effective when used in combination with sulfonylureas or insulin. These drugs include the alpha-glucosidase inhibitor acarbose ( Glucobay ); the biguanide metformin ( Diaformin , Glucophage ); the DPP-4 inhibitors alogliptin ( Nesina ), linagliptin ( Trajenta ), saxagliptin ( Onglyza ), sitaglip- tin ( Januvia ) and vildagliptin ( Galvumet , Galvus ); the glucagon-like peptide 1 liraglutide ( Victoza ) (not avail- able in New Zealand); the incretin mimetic exenatide ( Byetta ); the sodium-glucose co-transporters canagli- flozin ( Invokana ) and dapagliflozin ( Forxiga ); and the thiazolidinediones pioglitazone ( Actos ) and rosiglita- zone ( Avandia ) (see Table 38.3). Acarbose is an inhibitor of alpha-glucosidase (an enzyme that breaks down glucose for absorption); it delays the absorption of glucose. It has only a mild effect on glucose levels and has been associated with severe hepatic toxicity. It does not enhance insulin secretion, so its effects are additive to those of the sulfonylureas in controlling blood glucose. Alpha-glucosidase inhibitors are used in combination with sulfonylureas, metformin and insulin for individuals whose glucose levels cannot be controlled with a single agent or diet and exercise alone. Metformin decreases the production and increases the uptake of glucose. It is effective in lowering blood glucose levels and does not cause hypoglycaemia as the sulfonylureas do. It has been associated with the